Project I: During the first 5 years of the PHENIX project we have implemented a program for automated[unreadable] analysis of crystallographic data (mmtbx.xtriage), we have developed a highly automated program for[unreadable] anomalous substructure location (HySS), and we have created a new automated structure refinement[unreadable] program (phenix.refine). We have played an essential role in the birth of PHENIX by developing the open[unreadable] source C++ Computational Crystallography Toolbox (cctbx) and the PHENIX graphical user interface (GUI).[unreadable] We have worked closely with the other members of the PHENIX project to create an integrated system for[unreadable] automated structure determination that provides command-line interfaces, a visual programming interface,[unreadable] and the highly automated Wizard interface.[unreadable] We will use our strong foundation of computational algorithms and software to address some of the most[unreadable] challenging bottlenecks remaining in structure determination; classification of experimental data for decisionmaking,[unreadable] substructure location from weak signals, and productive and minimally-biased structure refinement[unreadable] at all resolution ranges. Our new algorithms which automatically assign a probability score to each dataset[unreadable] that describes the likelihood of successful structure solution will be used in subsequent decision-making by[unreadable] Projects II and IV. The result will be an increase in the efficiency of structure solution. The chances of[unreadable] successful substructure location will be improved by new algorithms for automated space group[unreadable] determination, optimal data cutoff calculation, and the application of improved likelihood scoring functions,[unreadable] developed in collaboration with Project III. This unique capability will make it possible for PHENIX to[unreadable] successfully-begin the process of structure solution, where other systems currently fail. We will develop new[unreadable] algorithms, including the use of normal models, for the refinement of models against experimental data at any[unreadable] resolution limit, by using automatic model parameterizations that maintain a reasonable ratio of parameters[unreadable] to observed data. We will also extend structure refinement to include algorithms for the local rebuilding of[unreadable] models, including peptide flips and rotamer refitting, in collaboration with Projects II and V. This approach will[unreadable] speed the convergence of refinement and reduce the need for manual intervention in many cases. Finally,[unreadable] we will enhance the PHENIX software by further development of our cctbx library, the PHENIX GUI, Project[unreadable] Data Storage, and the developer environment.[unreadable] Our new algorithms will enable researchers to determine the structures of challenging, high-value biological[unreadable] macromolecules which are important for understanding biology and ultimately improving human health.